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PXD022002

PXD022002 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleStructure of the human signal peptidase complex
DescriptionThe ER-resident signal peptidase complex (SPC) is an essential membrane protein complex involved in the maturation of soluble and type-I transmembrane proteins destined to the secretory pathway. As a part of the ER translocon machinery, the SPC removes signal peptides (SPs) from the N-termini of many proteins such as hormones, antibodies, or secretory enzymes1,2. To accomplish this task, the SPC must process a large variety of SPs with an exquisite specificity. Although the determinants of SP recognition have been established empirically3, the molecular details of SP recognition and removal remain elusive. Here, we show that the human SPC exists in two functional paralogs with distinct proteolytic subunits. We determined the structures and posttranslational modifications of both paralogs using electron cryo-microscopy and structural proteomics. The respective proteolytic subunits SEC11A and SEC11C adopt a conserved signal peptidase (SPase) fold with their active sites facing a prominent transmembrane window, which is collectively formed by the transmembrane domains of all SPC subunits. Characteristic, charged regions on both sides of this window locally thin the membrane by approximately 40% compared to the exterior. The data suggest a mechanistic model for SPC specificity and the transfer of SPs from the Sec61 translocation channel to the SPC.
HostingRepositoryPRIDE
AnnounceDate2021-07-05
AnnouncementXMLSubmission_2021-07-04_22:13:30.543.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterBarbara Steigenberger
SpeciesList scientific name: Bos taurus (Bovine); NCBI TaxID: 9913; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-10-15 03:55:39ID requested
12021-07-04 22:13:30announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Signal Peptidase Complex, cryoEM, Crosslinking MS
Contact List
Richard A. Scheltema
contact affiliationNetherlands Proteomics Centre, Biomolecular Mass Spectrometry and Proteomics
contact emailR.A.Scheltema@uu.nl
lab head
Barbara Steigenberger
contact affiliationBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University
contact emailB.A.Steigenberger@uu.nl
dataset submitter
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Dataset FTP location
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